MicroRNA-490-5P Targets CCND1 to Suppress Cellular Proliferation in Glioma Cells and Tissue Through Cell Cycle Arrest

Abstract

Background: Glioma is a type of tumor that starts in the glial cells of brain and spine. However, the underlying molecular mechanisms of miRNAs dysregulation in glioma initiation and progression is largely unclear.

Objective: To further understand the molecular mechanism of miR-490-5P functions and how miR-490 regulated CCND1 function.

Methods: The expression of miR-490-5P in glioma tissues and cells was measured by qRT-PCR and ISH. Cell transfection is responsible for miR-490-5P overexpression and knockdown. CCK-8 and clone formation assay are applicable to examine the capacity of glioma cells proliferation. Cell cycle analysis is used to test glioma cells cycle distribution with miR-490-5P overexpression or downregulation. Further, in vivo tumor exnograft studies are used to examine the effects of miR- 490-5P on glioma malignancy in vivo.

Results: We found overexpression of miR-490 lead to glioma cells cycle arrest at G1 phase and decreased proliferation. Next-step functional assays showed miR-490 regulated CCND1 expression and manipulated giloma cells proliferation. Finally, negative regulation of miR-490 in CCND1 function was validated through in vivo nude mice tumorigenesis assay and IHC examination in glioma tissue.

Conclusion: Overall, these results showed that epigenetic regulation of CCND1 via miR-490 was essential to glioma and provide a new insight into glioma diagnosis, treatment, prognosis and further translational investigations.

Keywords: CCND1; Epigenetic modificaiton; G1 phase arrest; Glioma; MiR-490; glioma cells..